Clinical Evaluation of the Relationship Between Systemic Disease and the Time of Onset of Peri-Implantitis: A Retrospective Cohort Study.

The role of systemic diseases in the development and progression of peri-implantitis remains unclear and requires discussion from various perspectives. This retrospective cohort study aimed to evaluate whether the type of systemic disease affects the onset time of peri-implantitis. The cohort consisted of patients who underwent implant maintenance evaluations between January 1998 and June 2020. Information on age, sex, history of periodontal disease, smoking habits, body mass index, systemic diseases, implant placement sites, and diagnosis of peri-implantitis were obtained. The relationships between the time of onset of peri-implantitis and the medical history of systemic diseases were determined statistically by applying the Kaplan-Meier analysis method and log-rank test. A total of 216 implants in 89 patients (34 male and 55 female) were included in this study. The average patient age was 53.9 ± 11.8 years at the first visit, and the mean duration of maintenance was 7 years and 4 months. A total of 43 patients had medical histories and were assigned to the systemic disease group. In this group, the overall prevalence of peri-implantitis was 25.4% (29 of 114 implants). The medical history of systemic diseases (odds ratio [OR], 6.87; 95% confidence interval [CI], 2.37-19.9) and dental history of periodontitis (OR, 3.64; 95% CI, 1.25-10.6) were assessed as risk factors for peri-implantitis. A significant difference in the time of onset of peri-implantitis was confirmed between patients with systemic disease and healthy patients. Diabetes mellitus, osteoporosis, and hypertension had a significant impact on the earlier onset of peri-implantitis.

Epstein-Barr Virus Promotes the Production of Inflammatory Cytokines in Gingival Fibroblasts and RANKL-Induced Osteoclast Differentiation in RAW264.7 Cells.

Periodontitis is an inflammatory condition that causes the destruction of the supporting tissues of teeth and is a major public health problem affecting more than half of the adult population worldwide. Recently, members of the herpes virus family, such as the Epstein-Barr virus (EBV), have been suggested to be involved in the etiology of periodontitis because bacterial activity alone does not adequately explain the clinical characteristics of periodontitis. However, the role of EBV in the etiology of periodontitis is unknown. This study aimed to examine the effect of inactivated EBV on the expression of inflammatory cytokines in human gingival fibroblasts (HGFs) and the induction of osteoclast differentiation. We found that extremely high levels of interleukin (IL)-6 and IL-8 were induced by inactivated EBV in a copy-dependent manner in HGFs. The levels of IL-6 and IL-8 in HGFs were higher when the cells were treated with EBV than when treated with lipopolysaccharide and lipoteichoic acid. EBV induced IκBα degradation, NF-κB transcription, and RAW264.7 cell differentiation into osteoclast-like cells. These findings suggest that even without infecting the cells, EBV contributes to inflammatory cytokine production and osteoclast differentiation by contact with oral cells or macrophage lineage, resulting in periodontitis onset and progression.

Methodological quality and risk-of-bias assessments in systematic reviews of treatments for peri-implantitis.

BACKGROUND AND OBJECTIVES: The purpose of the present study was to evaluate the methodological quality and risk of bias in systematic reviews (SRs) on the effectiveness of peri-implantitis treatments. MATERIAL AND METHODS: We searched four electronic databases: MEDLINE, Web of Science, Cochrane Database of Systematic Reviews, and EMBASE. Previous SRs focusing on peri-implantitis treatment published between 2010 and 2017 were identified. After literature screening, eligible SRs were qualitatively assessed using two validated instruments: Assessing the Methodological Quality of Systematic Reviews (AMSTAR2) and Risk Of Bias In Systematic reviews (ROBIS). The characteristics and findings of SRs are also reported. RESULTS: A total of 23 SRs formed the basis of this study. Of the 23, six included randomized controlled trials (RCTs) only. Overall, the AMSTAR2 assessment revealed three studies with high and six studies with low methodological quality, and all the other SRs were judged as having critically low methodological quality. ROBIS revealed only one Cochrane review with a low risk of bias and the others with a high risk of bias. In particular, the assessment of non-randomized studies (NRSIs), appropriateness of ROB assessment, and meta-analysis did not satisfy the criteria in AMSTAR2 assessment. Furthermore, there were a few SRs that interpreted and discussed the results of risk of bias (ROB) and heterogeneity assessment, together with the impact of treatment. CONCLUSIONS: Due to the lack of head-to-head comparisons conducted in RCTs, review authors need to use other sources of evidence, such as clinical control trials (CCTs), cohort studies (CS), clinical research (CR), and animal studies. The end result is the presentation of low-quality evidence, with high ROB. Several SRs conducted network meta-analysis as an alternative to head-to-head conventional meta-analysis of RCTs. We suggest that the best methods to generate, access, and assess evidence in situations where RCT evidence is lacking should be discussed on an urgent basis.

A Sinus Floor Reaugmentation Technique Around an Apically Exposed Implant Into the Maxillary Sinus.

Sinus floor augmentation (SFA) is the most predictable treatment option in the atrophic posterior maxilla. However, exposure of the apical implant body into the maxillary sinus cavity is an occasionally observed phenomenon after SFA. Although most penetrating dental implants remain completely asymptomatic, they may induce recurrent rhinosinusitis or implant loss. Removal of the implant should be considered if there is significant implant exposure that results in prolonged treatment and increased costs. This case report demonstrates a recovery approach using sinus floor reaugmentation without implant removal in a patient with an apically exposed implant into the maxillary sinus cavity.

Influence of estrogen deficiency on guided bone augmentation: investigation of rat calvarial model and osteoblast-like MC3T3-E1 cells.

The effect of estrogen deficiency in bone augmentation, and the mechanisms by which estrogen deficiency impedes osteoblast differentiation and collagen matrix production, were examined. Twenty female Jcl:Wistar rats were divided into two groups: ovariectomized rats; and control rats. Guided bone augmentation was performed by positioning plastic caps in the calvarium of all animals at 8 wk after ovariectomy or sham surgery. Micro-computed tomography and histological sections were used to determine the amount of bone augmentation within the plastic caps. At 8 wk, there was statistically significantly less newly formed bone volume in ovariectomized rats. Immunohistological staining revealed the rare alignment of runt-related transcription factor 2-positive osteoblast-like cells and collagen I-positive bundle fibers in ovariectomized rats. In cell culture experiments, pre-osteoblast-like cells, MC3T3-E1, were treated with the estrogen receptor antagonist, fulvestrant. In treated cells, alkaline phosphatase activity remained high, whereas Alizarin Red staining was completely inhibited. Extracellular staining intensity of collagen I was decreased after fulvestrant treatment. Consistent with these observations, gene-expression analysis confirmed that fulvestrant treatment led to weaker expression of mRNA for osteogenic transcription factors and bone matrix protein-related genes. The results demonstrate that estrogen deficiency suppresses osteoblast differentiation and collagen matrix production in bone augmentation.

Melatonin enhances vertical bone augmentation in rat calvaria secluded spaces.

BACKGROUND: Melatonin has many roles, including bone remodeling and osseointegration of dental implants. The topical application of melatonin facilitated bone regeneration in bone defects. We evaluated the effects of topical application of melatonin on vertical bone augmentation in rat calvaria secluded spaces. MATERIAL AND METHODS: In total, 12 male Fischer rats were used and two plastic caps were fixed in the calvarium. One plastic cap was filled with melatonin powder and the other was left empty. RESULTS: Newly generated bone at bone defects and within the plastic caps was evaluated using micro-CT and histological sections. New bone regeneration within the plastic cap was increased significantly in the melatonin versus the control group. CONCLUSIONS: Melatonin promoted vertical bone regeneration in rat calvaria in the secluded space within the plastic cap.

Effects of intermittent administration of parathyroid hormone on bone augmentation in rat calvarium.

OBJECTIVES: This study examined the effects of parathyroid hormone (PTH) on bone augmentation beyond the skeletal envelope within a plastic cap in rat calvaria. MATERIALS AND METHODS: The calvaria of 30 rats were exposed, and 2 plastic caps were placed on each. Each of the 10 rats was treated with 35 or 105 µg/kg (PTH-35, PTH-105) PTH 3 times per week. The control group was injected with sterile saline 3 times per week. Micro-computed tomography (CT) imaging was performed every 2 weeks for 12 weeks. Micro-CT and histological sections were used to determine the amount of bone augmentation within the plastic caps. Bone volume (BV) was calculated using BV-measuring software. RESULTS: The histomorphometric and histological analyses showed that the amount of bone augmentation was increased significantly in the PTH groups compared with the controls at 12 weeks. The PTH-105 group showed significantly more bone augmentation and osteoblasts compared with the PTH-35 group. CONCLUSIONS: These results indicate that the higher the dose of intermittent PTH administered, the greater the amount of bone formation beyond the skeletal envelop in the rat calvarium.

Orthodontic Implant Site Development Using Labial Root Torque: A Case Series with CBCT Analysis.

This case series assessed the efficacy of Orthodontic Implant Site Development with Labial Root Torque (OISD-LRT) as a nonsurgical technique for addressing labial bone deficiencies in seven patients. The procedure involved strategically placing a multi-bracket of 2-3 mm apically on the hopeless teeth, gradually shifting them with Ni-Ti wires at the rate of 2 mm per month and maintaining overcorrection for 2 months before extraction. OISD-LRT consistently augmented tissue for flapless guided implant surgery, with an average treatment duration of 404Å}311.7 days. Cone-beam computed tomography (CBCT) scans at various stages revealed increases in both vertical and horizontal bone dimensions, especially in the sockets with complete labial bone loss. Despite inevitable post-extraction reductions in bone height and width, sufficient dimensions were maintained to ensure long-term implant stability. This case series highlights the effectiveness of OISD-LRT as a valuable method for horizontal bone augmentation, particularly in patients with labial bone deficiency. This approach provides a robust foundation for subsequent implant placement, showcasing its success in addressing challenging anatomical conditions and contributing to the broader field of implant dentistry.

Staged Approach Involving Orthodontic Implant Site Development with Labial Root Torque and Guided Bone Regeneration; 3-Year Follow-up Case Report.

Restoring periodontally compromised teeth in aesthetic zones through dental implant rehabilitation poses significant challenges due to the loss of supporting tissues. This case report describes a staged treatment strategy designed for a 48-year-old woman with advanced chronic periodontitis of the aesthetic zone. This approach combined various advanced techniques, including periodontal regeneration, orthodontic implant site development with labial root torque, guided bone regeneration, and soft tissue augmentation. The innovative orthodontic implant site development with labial root torque technique was employed to harness healthy palatal periodontal ligament cells by strategically applying labial root torque in the horizontal labial-palatal direction. This technique uses healthy palatal periodontal ligament cells, which benefits overall periodontal health. The procedure involved gradually shifting hopeless teeth at a rate of 2 mm per month using nickel-titanium wires, thereby maintaining overcorrection for two months before extraction. Following successful orthodontic implant site development with labial root torque, the next phase involved guided bone regeneration using a honeycomb-structured titanium membrane. This set the stage for implant placement six months later, ensuring a stable foundation for subsequent prosthetic intervention. Soft tissue augmentation was then meticulously performed using an artificial collagen dermis infused with fibroblast growth factor-2, contributing to the overall aesthetic outcome. Final prosthesis integration revealed a harmonious blend with the adjacent teeth and gums, underscoring the success of this multidisciplinary approach. This case report provides valuable insights into severe periodontitis in the aesthetic field. Our findings highlight the importance of continuously researching and improving procedures for optimal patient care.

Resorbable bilayer membrane made of L-lactide-ε-caprolactone in guided bone regeneration: an in vivo experimental study.

PURPOSE: Guided bone regeneration (GBR) is an accepted method in dental practice that can successfully increase the bone volume of the host at sites chosen for implant placement; however, existing GBR membranes exhibit rapid absorption and lack of adequate space maintenance capabilities. We aimed to compare the effectiveness of a newly developed resorbable bilayer membrane composed of poly (L-lactic acid) and poly (-caprolactone) (PLACL) with that of a collagen membrane in a rat GBR model. METHODS: The rat calvaria was used as an experimental model, in which a plastic cylinder was placed. We operated on 40 male Fisher rats and subsequently performed micro-computed tomography and histomorphometric analyses to assess bone regeneration. RESULTS: Significant bone regeneration was observed, which was and similar across all the experimental groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, and sporadic partial degradation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. CONCLUSIONS: The PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane could address the limitations of the current membranes. Nevertheless, further studies and clinical trials are warranted to validate the efficacy and safety of The PLACL membrane in humans.

Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis.

Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation.

Micro-CT observation of angiogenesis in bone regeneration.

OBJECTIVES: Restoration of an adequate blood supply is essential for the bone healing process and is key to the success of bone augmentation procedures. In this study, we evaluated angiogenesis in rat calvarial flat bone defects using in vivo microfocus computed tomography (micro-CT). MATERIALS AND METHODS: Twenty rats were used. The calvarium was exposed and calvarial bone defects of critical (5-mm diameter) and non-critical (2.7-mm diameter) sizes were prepared. Bone regeneration and angiogenesis were evaluated by image analysis using micro-CT and histological examination. RESULTS: Critical- and non-critical-sized calvarial bone defects showed bone regeneration and angiogenesis around the midsagittal suture. Critical-sized calvarial bone defects showed approximately 1.2% reossification of the original surgical defect, whereas the non-critical-sized defects showed approximately 43.3% reossification at day 28. Furthermore, angiogenesis was observed later in the critical-sized calvarial bone defects (about 38.2%), whereas angiogenesis was observed early in the non-critical-sized calvarial bone defects (about 75.5%) at day 28. New blood vessel networks were observed around defects of both sizes. CONCLUSIONS: Angiogenesis preceded bone regeneration around critical- and non-critical-sized calvarial bone defects. Angiogenesis led to full bone formation in non-critical-sized defects.

Resorbable Membrane Pouch Technique for Single-Implant Placement in the Esthetic Zone: A Preliminary Technical Case Report.

The conventional protocol for lateral guided bone regeneration (GBR) in esthetic areas requires the securing of resorbable collagen membranes using titanium cortical bone pins to immobilize bone grafts. These procedures are highly invasive and can increase patient morbidity and discomfort. Herein, we introduce a minimally invasive novel resorbable membrane pouch technique, wherein collagen membranes can be immobilized by securing them to the periosteum without the need of titanium pins. We describe 11 cases of single-immediate- or delayed-implant placement in the atrophic maxilla esthetic zone. All implants were successful and functional without pain or inflammation and with optimal soft-tissue health and esthetics. Radiographic evaluation with cone-beam computed tomography (CBCT) and esthetic assessment using the pink esthetic score (PES) were performed. At the time of implant placement, the average augmented bone width was 2.8 ± 0.6 mm on CBCT analysis. In all cases, resorption of the augmented bone was confirmed with an average of -1.3 ± 0.8 mm. Soft-tissue outcomes were scored 1 year after permanent restoration. The PES score 1 year after treatment was 11.9 ± 1.4. The resorbable membrane pouch technique with immediate or delayed implant placement for buccal dehiscence in the esthetic area can be predictable and is minimally invasive.

Mild elevation of C-reactive protein in a young patient with severe periodontitis: a case report with 2 years of follow-up.

Periodontal inflammation is associated with systemic disease. Low-grade inflammation (LGI) is critical to the link between periodontal disease and several systemic disorders. C-reactive protein (CRP) is a common circulating biomarker for acute-phase immune responses, and it is closely related to LGI. The present case demonstrated excellent results using a comprehensive approach for periodontitis in a young woman with severe periodontitis and mild CRP elevation. A 21-year-old Japanese woman complained of tooth mobility and bleeding during tooth brushing. She was pre-obese (body mass index = 29.9), and she had a mildly elevated CRP level (5.2 mg/L). Of all periodontal sites, 34.5% had deep pockets (≥6 mm). The patient was diagnosed with stage III, grade C periodontitis and generalized aggressive periodontitis. Comprehensive periodontal treatments, including regenerative procedures for vertical bone loss and furcation involvement, were performed. Periodontal tissue inflammation was resolved, and periodontal regeneration was achieved. During the 2-year follow-up period, her teeth did not exhibit any signs of instability, attachment loss, or bone loss. Despite the weak nature of the evidence, this case suggests that CRP is valuable for assessing LGI, and it may potentially be considered during periodontal grading in the future.

Comparison of Macro-and Micro-porosity of a Titanium Mesh for Guided Bone Regeneration: An In Vivo Experimental Study.

BACKGROUND/AIM: Guided bone regeneration (GBR) is one of the surgical methods used for vertical ridge augmentation prior to dental implant placements. Titanium meshes have been used for osteogenic space maintenance in GBR sites by clinicians. We aimed to compare the influence of micropores and macropores in a titanium mesh on bone regeneration in a rat calvarial vertical GBR model. MATERIALS AND METHODS: The calvaria of nine rats were exposed, and plastic cylinders were set bilaterally. Eighteen surgical sites were randomly allocated into three groups according to the materials of titanium lid and bone substitutes: microporous titanium lid+deproteinized bovine bone mineral (DBBM), macroporous titanium lid +DBBM, microporous titanium lid+carbonate apatite. Newly generated bone inside the cylinders was evaluated using micro-computed tomography (micro-CT). Furthermore, bone regeneration and angiogenesis were evaluated histologically at 12 weeks. RESULTS: Quantitative volumetric analyses using micro-CT showed a gradual increase in bone volume inside the cylinders in all three groups. Histological observation confirmed vigorous bone regeneration in the microporous groups compared to that in the macroporous group. In the upper part of the cylinders, soft tissue invaded the GBR site by passing through the pores of the macroporous mesh. The blood vessels in the upper part of the cylinders were smaller in the microporous groups than in the macroporous group. There was no difference in bone formation between cylinders filled with DBBM or carbonate apatite. CONCLUSION: Microvasculature penetrates 50-µm diameter micropores and accelerates bone formation inside the cylinder, which was set on rat calvaria. The microporous titanium mesh can facilitate angiogenesis from both the dura mater and periosteal in vertical ridge augmentation. Our data showed superiority of microporous titanium vascular permeability and osteoconductivity, supporting bone growth.

Machine Learning in Predicting Tooth Loss: A Systematic Review and Risk of Bias Assessment.

Predicting tooth loss is a persistent clinical challenge in the 21st century. While an emerging field in dentistry, computational solutions that employ machine learning are promising for enhancing clinical outcomes, including the chairside prognostication of tooth loss. We aimed to evaluate the risk of bias in prognostic prediction models of tooth loss that use machine learning. To do this, literature was searched in two electronic databases (MEDLINE via PubMed; Google Scholar) for studies that reported the accuracy or area under the curve (AUC) of prediction models. AUC measures the entire two-dimensional area underneath the entire receiver operating characteristic (ROC) curves. AUC provides an aggregate measure of performance across all possible classification thresholds. Although both development and validation were included in this review, studies that did not assess the accuracy or validation of boosting models (AdaBoosting, Gradient-boosting decision tree, XGBoost, LightGBM, CatBoost) were excluded. Five studies met criteria for inclusion and revealed high accuracy; however, models displayed a high risk of bias. Importantly, patient-level assessments combined with socioeconomic predictors performed better than clinical predictors alone. While there are current limitations, machine-learning-assisted models for tooth loss may enhance prognostication accuracy in combination with clinical and patient metadata in the future.

Influence of antihypertensive medications on the clinical parameters of anodized dental implants: a retrospective cohort study.

BACKGROUND: Hypertension is a chronic medical condition in which blood pressure in the arteries is elevated. Given the large proportion of dental implant patients using antihypertensive medications, it is crucial to evaluate the effects of these drugs on the clinical parameters of osseointegrated implants. The aim of the present retrospective cohort study was to evaluate the influence of antihypertensive medications on clinical peri-implant tissue parameters. METHODS: Thirty-five patients received a total of 77 anodized dental implants. Based on the history of the use of antihypertensive medications, the patients were divided into two groups: the group taking antihypertensive medications (AH group) and the group of healthy patients (H group). Implants were followed up clinically and radiologically, with a focus on the peri-implant soft tissue parameters probing pocket depth, bleeding on probing, modified plaque index, and marginal peri-implant bone level stability. RESULTS: None of the implants were lost, and no technical failures occurred. The mean follow-up duration was 7 years and 1 month. A significant difference was observed in the probing pocket depth 3.8 ± 1.3 mm in the AH group and 3.0 ± 0.7 mm in the H group. In the AH and H groups, 26.5% (9/34) and 4.7% (2/43) of the patients were diagnosed with peri-implantitis at the implant level, respectively. CONCLUSIONS: Our findings suggest some correlations between antihypertensive medication use and clinical parameters in anodized peri-implant tissue.

CO2 Laser De-epithelization Technique for Subepithelial Connective Tissue Graft: A Study of 21 Recessions.

BACKGROUND/AIM: To report cases in which we achieved sufficient width of the keratinized gingiva using a coronally advanced flap in combination with a subepithelial connective tissue graft (SCTG) obtained by the 'CO2 laser de-epithelization technique' (CODE). PATIENTS AND METHODS: Eleven patients with 21 Miller Class I, II, and III gingival recessions had surgery. To prepare SCTG, free gingival grafts were harvested and de-epithelialized extra-orally. De-epithelialization was conducted by irradiation of CO2 laser. Postoperative examinations were performed at 12 months. RESULTS: At 12 months, statistically highly significant root coverage was achieved in all recessions. Complete root coverage was obtained in 7 of the 21 recessions. The treatment yielded mean root coverage of 41.0%, and was associated with a mean gain of keratinized gingiva of 2.9±0.3 mm. CONCLUSION: The use of CODE allows harvesting grafts of excellent quality and quantity and increases the keratinization of the overlying mucosal epithelium.

Pedicle Periosteum as a Barrier for Guided Bone Regeneration in the Rabbit Frontal Bone.

BACKGROUND/AIM: For alveolar ridge reconstruction prior to dental implant placement, a barrier membrane is placed to create space over the bone defect. Although periosteum possesses osteogenic capacity, direct contact between defects and periosteum has been avoided. The present study aimed to investigate whether pedicle periosteum could be used as a barrier membrane. MATERIALS AND METHODS: Twelve rabbits were used. A U-shaped incision was made in the frontal bone, and the skin-periosteum over the frontal bone was stripped. Two trephine-drilled holes with a diameter of 5 mm were prepared in the frontal bone. One hole was covered with pedicle periosteum (periosteum side), and the periosteum was secured to the contralateral side. The other defect was covered with an occlusive membrane (membrane side). RESULTS: The histological observation showed that both defects, which were covered either by the periosteum or by the membrane, were closed almost completely after 12 weeks of healing. No statistically significant difference was observed in the bone defect closure rates between the two sides at 4 and 12 weeks. CONCLUSION: This study demonstrated that the pedicle periosteum possesses regenerative effects equivalent to those of occlusive membrane. The periosteum contributes to new bone formation by acting as a mechanical barrier and a source of osteogenic components.

Enhancement of Bone Augmentation in Osteoporotic Conditions by the Intermittent Parathyroid Hormone: An Animal Study in the Calvarium of Ovariectomized Rat.

PURPOSE: Intermittent parathyroid hormone (PTH) is the commonly used therapeutic approach for patients with severe osteoporosis. The goal of this study was to elucidate the effect of the intermittent PTH treatment on guided bone augmentation (GBA) in the calvarium of ovariectomized (OVX) rats. MATERIALS AND METHODS: Surgical ovariectomy on 14 rats and sham surgery on 7 rats were conducted on all rats as the first surgery. GBA surgery was conducted 8 weeks following the first surgery in the rat calvarium by placing 5-mm-diameter cylindrical plastic caps. Following surgery, rats were treated with 40 µg/kg PTH (OVX-PTH) or saline (Sham-Saline, OVX-Saline) via intraperitoneal injection three times per week during the all-observational period. Longitudinal microcomputed tomography (micro-CT) imaging was performed every 2 weeks following the GBA surgery without euthanasia, and the amount of newly generated bone volume (BV) was calculated. All rats were euthanized 12 weeks after GBA surgery, and histology was obtained. Sections stained with hematoxylin and eosin were used for the quantitative analysis of newly generated tissue, and immunohistology was used to visualize Runx2-positive cells and TRAP-positive cells. RESULTS: Throughout the monitoring period, the BVs of OVX rats without PTH treatment (OVX-Saline) were significantly lower than that of the other two groups at weeks 8 and 12 in micro-CT analysis. During all experimental periods, the BV was highest in the OVX rats that were treated with PTH (OVX-PTH). Histologic analysis confirmed the result of micro-CT, and determined that the OVX-PTH presented a greater number of Runx2-positive cells. The number of TRAP-positive multinucleated osteoclasts was highest in OVX-PTH rats; there were no significant differences between the other two groups. CONCLUSION: The results of this study suggest that treatment with intermittent PTH was associated with increased newly regenerated bone volume in ovariectomized rat calvarial bone augmentation, which may have important clinical implications.